Hypermethylated TAGMe as a universal-cancer-only methylation marker and its application in diagnosis and recurrence monitoring of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. METHODS: The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. RESULTS: We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4-94.1%) and specificity of 90.0% (95% CI: 81.9-95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. CONCLUSION: TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021.

Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

Extracorporeal membrane oxygenation states basilar artery thrombectomy and left posterior cerebral artery stent thrombectomy: A case report.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a new type of extracorporeal respiratory and circulatory assistance device. It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator (membrane lung) to replace lung and heart functions in a short time. ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function. CASE SUMMARY: We report a case of an 81-year-old woman who underwent whole cerebral angiography, basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO. The patient was admitted to the hospital due to myocardial infarction. Considering that the cause of the patient's disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO, the department of Radioactive Intervention performed cerebral angiography. And the result of the angiography indicated vascular occlusion. After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain, the patency of the occlusive vessel was achieved. CONCLUSION: Although the patient eventually died of circulatory failure, the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.

Combined application of myo-inositol and corn steep liquor enhances seedling growth and cold tolerance in cucumber and tomato.

Low temperatures pose a common challenge in the production of cucumbers and tomatoes, hindering plant growth and, in severe cases, leading to plant death. In our investigation, we observed a substantial improvement in the growth of cucumber and tomato seedlings through the application of corn steep liquor (CSL), myo-inositol (MI), and their combinations. When subjected to low-temperature stress, these treatments resulted in heightened levels of photosynthetic pigments, thereby fostering enhanced photosynthesis in both tomato and cucumber plants. Furthermore, it contributed to a decrease in malondialdehyde (MDA) levels and electrolyte leakage (REP). The effectiveness of the treatment was further validated through the analysis of key gene expressions (CBF1, COR, MIOX4, and MIPS1) in cucumber. Particularly, noteworthy positive outcomes were noted in the treatment involving 0.6 mL L-1 CSL combined with 72 mg L-1 MI. This study provides valuable technical insights into leveraging the synergistic effects of inositol and maize leachate to promote early crop growth and bolster resistance to low temperatures.

Transition of cooking fuels and obesity risk in Chinese adults.

BACKGROUND: Since 1990 s, China has witnessed a widespread transition to clean cooking fuels, presenting an opportunity to investigate whether household fuel transition could mitigate obesity risk and reconcile inconsistencies in the literature regarding the association between cooking fuels and obesity. METHODS: The China Health and Nutrition Survey (CHNS) is a prospective cohort study covering 12 provinces of China (1989-2015). Participants were classified into persistent cleaner fuel users, fuel transitioners, and persistent polluting fuel users according to self-reported primary cooking fuels. Obesity and central obesity were defined as BMI ≥ 28.0 kg/m2 and waist circumference ≥ 90 cm in men and ≥ 85 cm in women according to Chinese criteria. FINDINGS: Among 13,032 participants, 3657 (28.06 %) were persistent cleaner fuel users; 5264 (40.39 %) transitioned from using polluting fuels to cleaner fuels after the baseline survey; and 4111 (31.55 %) were persistent polluting fuel users. During the period of follow-up of 9.0 ± 6.8 years, 1248 (9.58 %) participants were classified into the obesity category, and 4703 (36.09 %) into the central obesity category. Persistent polluting fuel users had a significantly higher risk of developing obesity (hazard ratio [HR]: 1.45, 95 %CI: 1.22-1.72) and central obesity (HR: 1.32, 95 %CI: 1.21-1.44), compared to persistent cleaner fuel users. Persistent polluting fuel use was positively associated with developing obesity in women (HR: 1.64, 95 %CI: 1.30-2.06), but not in men. Subgroup analyses showed higher HR of persistent polluting fuel use among individuals aged 18-44 years (HR: 2.04, 95 %CI: 1.62-2.56). In contrast, the transitioners did not exhibit a significantly different risk of developing obesity (HR: 0.94, 95 %CI: 0.80-1.10) compared to persistent cleaner fuel users, which was consistent across different sex, age and urbanicity. Similar trends were observed for developing central obesity. INTERPRETATION: Persistent polluting fuel use increased obesity risk while the obesity risk of the transition to cleaner fuels was similar to persistent use of cleaner fuels. The finding underscores the significance of advocating for the adoption of cleaner fuels as a strategy to mitigate the disease burden associated with obesity.

UPLC-MS/MS determination of 71 neuropsychotropic drugs in human serum.

In this study, a UPLC-MS/MS method was developed for the rapid detection of 71 neuropsychotropic drugs in human serum for drug concentration monitoring and toxicity screening. The analytes were separated from the biological matrix by protein precipitation using a methanol-acetonitrile solvent mixture. The chromatographic separation was performed on a Kromasil ClassicShell C18 column (2.1*50 mm, 2.5 µ m) with gradient elution using acetonitrile-0.2 % acetic acid and 10 mM ammonium acetate as the mobile phases (flow rate 0.4 mL/min, column temperature 40 °C, injection volume 5 µL). An electrospray ion source in both positive and negative ion modes with multiple ion monitoring was used. The total run time was 6 min. All compounds were quantified using the isotope internal standard method. Totally, 71 drugs were detected within their linear ranges with correlation coefficients greater than 0.990. The intra- and inter-batch precision relative standard deviations (RSDs) for the low, medium, and high concentration points were less than 15 %, with an accuracy of 90%-110 %. All compounds except Moclobemide N-oxindole are stabilised within 7 days. The relative matrix effect results for each analyte were within ±20 % of the requirements. The method is validated according to Clinical and Laboratory Standards Institute guidelines, easy to use, and has a low cost.

High-throughput screen identifies non inflammatory small molecule inducers of trained immunity.

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite its promise for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as ß-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. This limited collection of training compounds also limits the study of the genes most involved in training responses as each molecule has both training and nontraining effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future applications. To identify small molecule inducers of trained immunity, we screened a library of 2,000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over two dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation-a current limitation of reported inducers of training. A surprising result was the identification of glucocorticoids, traditionally considered immunosuppressive, providing an unprecedented link between glucocorticoids and trained innate immunity. We chose seven of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating alternative avenues for studying and applying innate immune training.

Chondroitin Sulfate-Modified Hydroxyapatite for Caspase-1 Activated Induced Pyroptosis through Ca Overload/ER Stress/STING/IRF3 Pathway in Colorectal Cancer.

Immune checkpoint inhibitors, are the fourth most common therapeutic tool after surgery, chemotherapy, and radiotherapy for colorectal cancer (CRC). However, only a small proportion (≈5%) of CRC patients, those with "hot" (immuno-activated) tumors, benefit from the therapy. Pyroptosis, an innovative form of programmed cell death, is a potentially effective means to mediate a "cold" to "hot" transformation of the tumor microenvironment (TME). Calcium-releasing hydroxyapatite (HAP) nanoparticles (NPs) trigger calcium overload and pyroptosis in tumor cells. However, current limitations of these nanomedicines, such as poor tumor-targeting capabilities and insufficient calcium (Ca) ion release, limit their application. In this study, chondroitin sulfate (CS) is used to target tumors via binding to CD44 receptors and kaempferol (KAE) is used as a Ca homeostasis disruptor to construct CS-HAP@KAE NPs that function as pyroptosis inducers in CRC cells. CS-HAP@KAE NPs bind to the tumor cell membrane, HAP released Ca in response to the acidic environment of the TME, and kaempferol (KAE) enhances the influx of extracellular Ca, resulting in intracellular Ca overload and pyroptosis. This is associated with excessive endoplasmic reticulum stress triggered activation of the stimulator of interferon genes/interferon regulatory factor 3 pathway, ultimately transforming the TME from "cold" to "hot".

Photocarrier tunneling triggering CO2 photocatalysis.

Solar CO2 reduction to renewable hydrocarbon fuels offers a promising pathway to carbon neutrality, but it is retarded by tough CO2 activation, complicated mechanisms, sluggish charge transport kinetics, and a scarcity of strategies for precise tuning of charge transport pathways. Herein, we first conceptually design a novel insulating polymer-mediated electron-tunneling artificial photosystem via progressive interface configuration regulation, wherein tailor-made Ag@citrate nanocrystals (NCs) are controllably self-assembled on transition metal chalcogenides (TMCs) assisted by an ultrathin insulating polymer interim layer, i.e., poly(allylamine hydrochloride) (PAH). In this multilayered nano-architecture, a solid ultra-thin insulating PAH interim layer serves as an unexpected charge tunneling mediator to stimulate smooth electron transfer from the TMC substrate to the terminal electron reservoirs of Ag@citrate NCs, engendering the tandem charge transfer route and significantly boosting the visible-light-driven photocatalytic CO2-to-syngas conversion performances. Furthermore, we have ascertained that such TMC-insulating polymer-metal NC tunneling photosystems are universal. This study would spark new inspiration for unleashing the long-term neglected charge tunneling capability of insulating polymers and diversifying non-conjugated polymer-based artificial photosystems for solar-to-fuel energy conversion.

Genome-Wide Analysis of Polygalacturonase Gene Family Reveals Its Role in Strawberry Softening.

Fruit softening is a prominent attribute governing both longevity on shelves and commercial worth. Polygalacturonase (PG) plays a major role in strawberry fruit softening. However, the PG gene family in strawberry has not been comprehensively analyzed. In this study, 75 FaPG genes were identified in the octoploid strawberry genome, which were classified into three groups according to phylogenetic analysis. Subcellular localization prediction indicated that FaPGs are mostly localized to the plasma membrane, cytoplasm, and chloroplasts. Moreover, the expression of FaPGs during strawberry development and ripening of 'Benihoppe' and its softer mutant was estimated. The results showed that among all 75 FaPGs, most genes exhibited low expression across developmental stages, while two group c members (FxaC_21g15770 and FxaC_20g05360) and one group b member, FxaC_19g05040, displayed relatively higher and gradual increases in their expression trends during strawberry ripening and softening. FxaC_21g15770 was selected for subsequent silencing to validate its role in strawberry softening due to the fact that it exhibited the highest and most changed expression level across different developmental stages in 'Benihoppe' and its mutant. Silencing FxaC_21g15770 could significantly improve strawberry fruit firmness without affecting fruit color, soluble solids, cellulose, and hemicellulose. Conversely, silencing FxaC_21g15770 could significantly suppress the expression of other genes related to pectin degradation such as FaPG-like, FaPL, FaPME, FaCX, FaCel, FaGlu, FaXET, and FaEG. These findings provide basic information on the FaPG gene family for further functional research and indicate that FxaC_21g15770 plays a vital role in strawberry fruit softening.

Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

Spatially confined synthesis of large-sized MoS2nanosheets in molten KSCN toward efficient hydrogen evolution.

Low-temperature KSCN molten salt is a promising technique to synthesize defect-rich MoS2catalysts for hydrogen evolution reaction (HER). However, owing to the fast ion diffusion rate for rapid crystal growth, the resultant catalysts show a morphology of microsphere, which aggregates from MoS2nanosheets, to suppress the catalytic performance. In this work, large-sized few-layer MoS2nanosheets are synthesized via a spatial confinement strategy by adding inert NaCl into the KSCN molten salt. With the NaCl spacer to physically block the long-distance ion diffusion and isolate the chemical reaction, the MoS2nucleation and subsequent crystal growth could be controlled, guiding the nanosheets to grow along the narrow gap between the NaCl crystals to avoid aggregation. As a result, ultrathin MoS2nanosheets with a large geometry size are constructed. Profiting from the architecture to expose active sites and boost charge transfer kinetics, the large-sized few-layer MoS2nanosheets exhibit an impressive HER performance, showing a smallη10of 160 mV and a low Tafel slope of 53 mV dec-1with excellent stability. This work provides not only an efficient HER catalyst but also a facile spatial confinement technique to design and synthesize a large spectrum of transition metal sulfides for broad uses.

Sustainable versatile chitin aerogels: facile synthesis, structural control and high-efficiency acoustic absorption.

Bio-based materials with excellent acoustic absorption properties are in great demand in architecture, interior, and human settlement applications for efficient noise control. In this study, crayfish shells, a form of kitchen waste, are utilized as the primary material to produce ultralight and multifunctional chitin aerogels, which effectively eliminate noise. Different replacement solvents and freezing rates were employed to regulate the porous structures of chitin aerogels, and their resulting acoustic absorption performance was investigated. Results demonstrate that employing deionized water as the replacement solvent and utilizing a common-freeze mode (frozen via refrigerator at -26 °C) can produce chitin aerogels with larger porosity (96.26%) and apertures, as well as thicker pore walls. This results in superior broadband acoustic absorption performance (with a maximum absorption coefficient reaching 0.99) and higher Young's modulus (28 kPa). Conversely, chitin aerogels solvent-exchanged with tert-butyl alcohol or subjected to quick-freeze mode (frozen via liquid nitrogen) exhibit smaller porosity (92.32% and 94.84%) and apertures, thereby possessing stronger diffuse reflection of visible light (average reflectance of 94.30% and 88.18%), and enhanced low-frequency (500 to 1600 Hz) acoustic absorption properties. Additionally, the acoustic absorption mechanism of fabricated chitin aerogels was predicted using a simple three-parameter analysis Johnson-Champoux-Allard-Lafarge (JCAL) model. This study presents a novel approach to developing multifunctional biomass materials with excellent acoustic absorption properties, which could have a wide range of potential applications.

Integrating Multiple Bacterial Phenotypes and Bayesian Network for Analyzing Health Risks of Pathogens in Plastisphere.

Plastic pollution represents a critical threat to soil ecosystems and even humans, as plastics can serve as a habitat for breeding and refuging pathogenic microorganisms against stresses. However, evaluating the health risk of plastispheres is difficult due to the lack of risk factors and quantification model. Here, DNA sequencing, single-cell Raman-D2O labeling, and transformation assay were used to quantify key risk factors of plastisphere, including pathogen abundance, phenotypic resistance to various stresses (antibiotic and pesticide), and ability to acquire antibiotic resistance genes. A Bayesian network model was newly introduced to integrate these three factors and infer their causal relationships. Using this model, the risk of pathogen in the plastisphere is found to be nearly 3 magnitudes higher than that in free-living state. Furthermore, this model exhibits robustness for risk prediction, even in the absence of one factor. Our framework offers a novel and practical approach to assessing the health risk of plastispheres, contributing to the management of plastic-related threats to human health.

The trend analysis of HIV and other sexually transmitted infections among the elderly aged 50 to 69 years from 1990 to 2030.

Background: The HIV and other sexually transmitted infections (STI) excluding HIV among the elderly population urgently require more attention and in-depth study. We aimed to present and predict the worldwide of its burden from 1990 to 2030 using data from the Global Burden of Disease (GBD) study. Methods: Leveraging the 2019 GBD study, we investigated the average annual percentage change (AAPC) of HIV and other STI in incidence, prevalence, disability-adjusted life years (DALYs), and mortality rates for individuals aged 50-69 across different age groups, genders, sociodemographic index (SDI) regions, and nations. The incidence of STI in the population from 2020 to 2030 was explored by Bayesian age-period-cohort (BAPC) prediction model. Results: The HIV incidence rate experienced its fastest growth 1990-1992, peaked in 1996, and gradually declined thereafter, with the 2019 rate being lower than that of 1990. The prevalence rate didn't present a sharp turning point. After 2006, its growth rate accelerated. Both DALYs and mortality rates plateaued high between 2002 and 2005, followed by a decline. The decline was steepest from 2005-2012, yet the rate of decrease slowed noticeably from 2012-2019.When segmented by age, HIV was more prevalent among those aged 55-59 and 50-54, with the 50-54 age group witnessing the fastest decline in incidence rates. However, the fastest growth in prevalence rates was seen among the 60-64 and 65-69 age groups. The other STI incidence rate declined from 1990-1996, increased up to 2006, declined until 2015, and then saw a resurgence with accelerated growth thereafter. The prevalence rate showcased varied trends, with a notable increase in the past five years. The highest growth in incidence rate was among the 65-69 age group. We predict that the incidence rate of STI will increase in the future. Conclusions: Overall, despite the evident decline in incidence, mortality rates, and DALYs, the prevalence of HIV and other STI among the elderly is rising, and both demonstrated significant trend variations across different ages, genders, SDI regions, and nations. Comprehensive sexual health education, clinical care and adjustments in health service strategies based on the evolving trends of HIV and other STI among the elderly are paramount.

Depressive symptoms of older adults with chronic diseases: the mediating roles of activities of daily living and economic burden of diseases.

Objective: To explore the mediating roles of activities of daily living (ADL) and economic burden of diseases in the relationship between chronic diseases and depressive symptoms of older adults. Methods: The data were sourced from China Health and Retirement Longitudinal Study (CHARLS). The number of chronic diseases, ADL, out-of-pocket medical expenses and the Center for Epidemiological Studies Depression Scale (CES-D) were selected as measuring indexes. Mediation analysis was conducted to explore the potential mediating roles of ADL and economic burden of diseases in the association between chronic diseases and depressive symptoms. Results: The number of chronic diseases, ADL, economic burden of diseases and depressive symptoms of older adults were significantly correlated with each other. ADL and economic burden of diseases individually mediated the relationship between the number of chronic diseases and depressive symptoms, accounting for 31.460% and 5.471% of the total effect, respectively. Additionally, ADL and economic burden of diseases demonstrated a chain mediating effect in this relationship, contributing to 0.759% of the total effect. Conclusion: The chain-mediated model effectively elucidated the mediating roles of ADL and economic burden of diseases in the association between chronic diseases and depressive symptoms among older adults. The study underscores the need for policymakers to focus attentively on the mental health of older adults with chronic diseases. Enhancing the capacity for ADL and strengthening social security to mitigate the economic burden of diseases are recommended strategies to alleviate depressive symptoms in older adults.

Prognostic Impact of Tumor-Infiltrating Immune Cells on Efficacy of Neoadjuvant Chemotherapy in Patients with Advanced or Metastatic Ovarian Cancer: A Retrospective Study.

BACKGROUND Tumor-infiltrating immune cells (TIICs) are implicated in the survival of ovarian cancer (OVCA) patients, but their prognostic significance in advanced or metastatic OVCA patients treated with neoadjuvant chemotherapy (NCAT) has not been well documented, particularly in the Chinese population. MATERIAL AND METHODS A total of 31 advanced or metastatic OVCA patients who underwent NACT were included. The density and positive rate of tumor-infiltrating immune cells (TIICs) within cancer cell nests and in cancer stroma were explored. The correlations of pre- or post-NACT TIICs with the efficacy of NACT and the changes in TIIC subpopulation with NACT were examined. RESULTS Compared with patients with partial benefit from NACT, significantly decreased pre-NACT intratumoral CD68⁺CD163⁺ cells (P=0.0043) and increased pre-NACT intratumoral CD56⁺ cells (P=0.038) were observed in patients with benefit. The high level of pre-NACT intratumoral CD68⁺CD163⁻ M1 macrophage (P=0.075) and stromal CD3⁺PD-1⁺ cells (P=0.085) predicated improved progression-free survival, respectively. Increased post-NACT stromal CD68⁺CD163⁻ M1 macrophage (P=0.01), stromal CD8⁺ T cells (P=0.073), and stromal CD8⁺PD-1⁺ cells (P=0.072) were associated with benefit from NACT. Moreover, NACT increased intratumoral CD3⁺ (P=0.031), CD8+ (P=0.031), and CD3⁺CD8⁺ cells (P=0.031). CONCLUSIONS High intratumoral CD68⁺CD163⁻, intratumoral CD56⁺ cells, and stromal CD3⁺PD-1⁺ cells pre-NACT predicted good prognosis. Intratumoral CD3⁺, CD8⁺, and CD3⁺CD8⁺ cells were increased after NACT. Evaluation of immune profiles may help to identify patients who might benefit from NACT and allow us to further stratify advanced or metastatic OVCA patients treated with NACT for disease management.

Novel anthropometric indices are superior adiposity indexes to portend visual impairment in middle-aged and older Chinese population.

OBJECTIVE: To investigate differential associations of traditional and novel adiposity indices with visual impairment (VI) in the middle-aged and older Chinese population. METHODS AND ANALYSIS: Based on the China Health and Retirement Longitudinal Study, 7750 Chinese older adults aged over 45 were included at baseline 2011, and 4133 participants who accomplished all three interviews from 2011 to 2015 were adapted for longitudinal analyses. We enrolled six adiposity indices, including the body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), a body shape index (ABSI), body roundness index (BRI) and conicity index (ConI). Visual status and other covariates included sociodemographic characteristics, medical supports and lifestyle-related factors. Cross-sectional correlations were assessed using univariate and multivariate logistic regression analyses. For longitudinal analysis, generalised linear models with generalised estimating equations were used to determine the association between time-varying adiposity and visual status. RESULTS: Higher levels of WHtR/WWI/ABSI/BRI/ConI were significantly associated with an increased prevalence of VI, whereas a higher BMI was associated with a decreased prevalence of VI. Only WWI was significantly related to the prevalence of VI after adjustment for multiple confounders in both cross-sectional and longitudinal analyses (all p values <0.05). The multivariable-adjusted OR (95% CI) of VI associated with the highest (vs lowest) quintile of WWI was 1.900 (1.407 to 2.565). CONCLUSION: WWI is a reliable alternative adiposity index that exhibits a dose-response association with the prevalence of VI in the Chinese population. The WWI-VI correlation may eliminate the obesity paradox in the ophthalmic epidemiological area and indicate the detrimental impact of changes in body composition on VI.

Evidence of abnormal hot carrier thermalization at van Hove singularity of twisted bilayer graphene.

Interlayer twist evokes revolutionary changes to the optical and electronic properties of twisted bilayer graphene (TBG) for electronics, photonics and optoelectronics. Although the ground state responses in TBG have been vastly and clearly studied, the dynamic process of its photoexcited carrier states mainly remains elusive. Here, we unveil the photoexcited hot carrier dynamics in TBG by time-resolved ultrafast photoluminescence (PL) autocorrelation spectroscopy. We demonstrate the unconventional ultrafast PL emission between the van Hove singularities (VHSs) with a ∼4 times prolonged relaxation lifetime. This intriguing photoexcited carrier behavior is ascribed to the abnormal hot carrier thermalization brought by bottleneck effects at VHSs and interlayer charge distribution process. Our study on hot carrier dynamics in TBG offers new insights into the excited states and correlated physics of graphene twistronics systems.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.